Interactions between Calcium Channel Blockers and Non‐Cardiovascular Drugs: Interactions with Anticancer Drugs

Baeyens, José M.

doi:10.1111/j.1600-0773.1988.tb00899.x

Cited by 11 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6. Apparently, the inhibition of the slow calcium influx as a physiological effect of the calcium antagonists plays no crucial part in the reversal of multi drug resistance [5,29],…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, a range of so-called 'chemosensitizing agents' (table 1) has been identified which enhances the antitumorous efficacy of cytotoxic medicaments such as the vinca-alkaloids or the anthracyclines in vitro by inac tivation of the transmembraneous efflux [5,6]. Although most of these substances cannot be applied to human beings for the purpose of reversing MDR for reason of their pharmacological or toxological properties, initial clinical trials on some tumors with verapamil [7][8][9][10] derivatives such as nitrendipine (NIT), nimodipine (NIM) and the new R-stereoisomer of verapamil (R-VPM).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circumvention of Multidrug Resistance Mediated by P-170 Glycoprotein Using Calcium Antagonists in Primary Human Renal Cell Carcinoma

et al. 1991

View full text Add to dashboard Cite

In experimental cell lines and in some human tumors, calcium antagonists reversed multidrug resistance mediated by P-170 glycoprotein in vitro. So far, clinical trials have not been very rewarding as intrinsic cardiovascular activites of these compounds impeded sufficient dosage. Renal cell carcinomas are considered to be good models for the evaluation of this new therapeutic concept. In 35 primary human renal cell carcinomas, the potency of 7 different calcium antagonists in combination with vinblastine monotherapy was examined in a tetrazolium-based microculture assay (MTT test) in order to circumvent chemoresistance. Concomitantly, P-170 glycoprotein expression was traced immunohistochemically using moab C 219. Substances derived from piperazine (flunarizine) showed only minor effects in this respect. The calcium antagonists of the papaverine type such as verapamil etc. revealed the strongest reversal of chemoresistance. Derivatives of benzothiazepine (diltiazem) or of dihydropyridine (nifedipine etc.) acted similarly and reached about 70% of the verapamil activity. All calcium antagonists lead to a significant enhancement of vinblastine cytotoxicity. An obvious link of P-170 glycoprotein to vinblastine chemoresistance was demonstrated. This particular resistance characteristic was detected in 19 of 27 resistant cases, but in none of the tumors displaying a chemoresponse. In particular, the new stereoisomer R-verapamil, which showed strong reversal of chemoresistance but which exerts 10 times lower cardiovascular side effects than racemic verapamil, seems to be suitable for further evaluation with regard to the clinical application.

show abstract

“…6. Apparently, the inhibition of the slow calcium influx as a physiological effect of the calcium antagonists plays no crucial part in the reversal of multi drug resistance [5,29],…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circumvention of Multidrug Resistance Mediated by P-170 Glycoprotein Using Calcium Antagonists in Primary Human Renal Cell Carcinoma

et al. 1991

View full text Add to dashboard Cite

show abstract

“…5. Sicher ist, daß die Blockade des langsamen Kalziumeinstroms als physiologische Wirkung der Kalziumantagonisten keine Rolle bei der Überwindung von Vielfach-Resistenz spielt (1,16).…”

Section: Diskussionunclassified

“…1), die durch Behinderung des transmembranösen Effluxes die antitumorale Wirkung klassischer Chemotherapeutika, wie z.B. der Vinca-Alkaloide oder der Anthrazykline, in vitro erhöhen können (1,17). Obwohl die meisten dieser Substanzen aufgrund ihrer pharmakologischen oder toxikologischen Eigenschaften für eine Verwendung als Resistenzdurchbrecher beim Menschen nicht in Betracht kommen, liegen bereits erste klinische Ergebnisse mit Verapamil (2,23,24,27), Chinidin (7), Amiodaron (7) und Amphotericin B (29) bei einigen Tumorarten vor.…”

unclassified

Chemoresistenz des Nierenzellkarzinoms: Stellenwert der Kalziumantagonisten

Mickisch¹,

Kössig²,

Tschada³

et al. 1990

Aktuel Urol

View full text Add to dashboard Cite

Effects of clonidine‐induced hypotension and dopamine‐induced hypertension on blood flows in prostatic adenocarcinoma (dunning R3327) and normal tissues

et al. 1992

View full text Add to dashboard Cite

In the present study it was investigated whether hypertension induced by dopamine or hypotension induced by clonidine could influence the relative blood distribution in a s.c. transplanted prostatic adenocarcinoma in relation to blood flow in normal tissues in rats. The blood flow was measured by using a radioactive microspheres technique. A bolus injection of 5 micrograms clonidine caused a decrease in the systemic blood pressure with 15-45 mm Hg, and blood flow to the central parts of the tumor, decreased with more than 50%. In the prostate, testes and ileo-psoas muscle a similar reaction was seen. During an infusion of 95-120 micrograms/kg/min dopamine, the blood pressure increased with 15-30 mm Hg, but the blood flow to the tumor was unchanged. However, in the testes and kidneys a decreased blood flow was observed. Moreover, mean blood flow to the central parts of the tumor decreased with increase in tumor size. The results further indicated that hyper- or hypotension or concomitantly given vasoactive drugs with the specific cancer treatment can have unwarranted effects on the distribution of cytotoxic drugs and oxygenation of the tumor.

show abstract

Interactions between Calcium Channel Blockers and Non‐Cardiovascular Drugs: Interactions with Anticancer Drugs

Cited by 11 publications

References 25 publications

Circumvention of Multidrug Resistance Mediated by P-170 Glycoprotein Using Calcium Antagonists in Primary Human Renal Cell Carcinoma

Circumvention of Multidrug Resistance Mediated by P-170 Glycoprotein Using Calcium Antagonists in Primary Human Renal Cell Carcinoma

Chemoresistenz des Nierenzellkarzinoms: Stellenwert der Kalziumantagonisten

Effects of clonidine‐induced hypotension and dopamine‐induced hypertension on blood flows in prostatic adenocarcinoma (dunning R3327) and normal tissues

Contact Info

Product

Resources

About